Fluoroscopy apparatus, fluoroscopy system, and fluorescence-image processing method

ABSTRACT

Observation is performed with a fluorescence image having high quantitativeness by satisfactorily eliminating dependency on distance. Provided is a fluoroscopy apparatus including an illumination unit having a light source that radiates illumination light and excitation light onto an observation target site, a fluorescence-imaging unit that acquires a fluorescence image by imaging fluorescence generated at the observation target site by the radiation of excitation light, a white-light-imaging unit that acquires a reference image by imaging return light returning from the observation target site by the radiation of the illumination light, and an image-correction unit that obtains a correction fluorescence image by raising the luminance value of the fluorescence image to the power of a reciprocal of a first exponent obtained by a power approximation of a distance characteristic of luminance versus observation distance, for the fluorescence image, that obtains the correction reference image by raising the luminance value of the reference image to the power of a reciprocal of a second exponent obtained by a power approximation of a distance characteristic of luminance versus observation distance, for the reference image, and that obtains a corrected fluorescence image by dividing the correction fluorescence image by the correction reference image.

CROSS REFERENCE TO RELATED APPLICATIONS

This is a continuation of International Application PCT/JP2010/054510,with an international filing date of Mar. 17, 2010, which is herebyincorporated by reference herein in its entirety. This applicationclaims the benefit of Japanese Patent Application No. 2009-072852, thecontent of which is incorporated herein by reference.

TECHNICAL FIELD

The present invention relates to a fluoroscopy apparatus, a fluoroscopysystem, and a fluorescence-image processing method.

BACKGROUND ART

In the related art, there is a known fluoroscopy apparatus that iscapable of obtaining a high-luminance fluorescence image of a lesion byradiating excitation light, which excites fluorescent dye to generateagent-fluorescence, onto an observation target site, to which afluorescent dye that specifically accumulates at a lesion, such ascancer cells, is administered, and by capturing the agent-fluorescencegenerated (for example, see Patent Literature 1).

In the fluoroscopy apparatus described in Patent Literature 1, since theintensity of the excitation light radiated onto an observation targetsite varies depending on distance, in order to correct the influence dueto the distance, arithmetic processing in which a fluorescence image ofthe observation target site is divided by a reflected-light image of thesame observation target site is performed.

Citation List

{Patent Literature}

-   {PTL 1} Japanese Unexamined Patent Application, Publication No. Sho    62-247232.

SUMMARY OF INVENTION

The present invention employs the following solutions.

A first aspect of the present invention is a fluoroscopy apparatusincluding, an illumination portion having a light source that radiatesillumination light and excitation light onto a subject, afluorescence-imaging unit that acquires a fluorescence image by imagingfluorescence generated at the subject by the radiation of the excitationlight from the illumination portion, a return-light imaging unit thatacquires a reference image by imaging return light returning from thesubject by the radiation of the illumination light from the illuminationportion, and an image-correction unit that corrects the fluorescenceimage acquired by the fluorescence-imaging unit by using the referenceimage acquired by the return-light imaging unit, wherein in theimage-correction unit, a correction fluorescence image is obtained byraising a luminance value of the fluorescence image to the power of thereciprocal of a first exponent that is obtained by a power approximationof a characteristic of luminance versus distance from the illuminationportion to the subject, for the fluorescence image acquired by thefluorescence-imaging unit when the excitation light of a prescribedintensity is radiated towards the subject; a correction reference imageis obtained by raising a luminance value of the reference image to thepower of the reciprocal of a second exponent that is obtained by a powerapproximation of a characteristic of luminance versus distance from theillumination portion to the subject, for the reference image obtained bythe return-light imaging unit when the illumination light of aprescribed intensity is radiated towards the subject; and a correctedfluorescence image is obtained by dividing the correction fluorescenceimage by the correction reference image.

According to this aspect, by radiating the excitation light emitted fromthe illumination portion onto the subject, the fluorescence generated atthe subject is imaged by the fluorescence-imaging unit imaging unit anda fluorescence image is acquired, and by radiating the illuminationlight emitted from the illumination portion together with the excitationlight onto the subject, the return light thereof is imaged by thereturn-light imaging unit and a reference image is acquired.

In this case, the fluorescence image acquired by thefluorescence-imaging unit contains information related to thefluorescence that is raised to the power of the distance from theillumination portion to the subject, and the reference image acquired bythe return-light imaging unit contains information related to theillumination light that is raised to the power of the distance from theillumination portion to the subject. In addition, because thefluorescence and return-light characteristics differ if they areinfluenced by internal scattering, surface reflection, or the like, thecharacteristic of the luminance of the fluorescence image on thedistance from the illumination portion to the subject differs from thecharacteristic of the luminance of the reference image on the distancefrom the illumination portion to the subject.

According to the fluoroscopy apparatus of the present invention, in theimage-correction unit, by raising the luminance value of thefluorescence image to the power of the reciprocal of the first exponentobtained by a power approximation of the characteristic of the luminanceversus distance from the illumination portion to the subject, for thefluorescence image, it is possible to obtain the correction fluorescenceimage having a substantially constant luminance relative to variationsin the distance. In addition, by raising the luminance value of thereference image to the power of the reciprocal of the second exponentobtained by a power approximation of the characteristic of the luminanceof versus distance from the illumination portion to the subject, for thereference image, it is possible to obtain the correction reference imagehaving a substantially constant luminance relative to the variations ofthe distance. Therefore, by dividing the correction fluorescence imageby the correction reference image, it is possible to obtain a correctedfluorescence image having quantitativeness, in which the dependencies ofthe fluorescence image and the reference image on distance are cancelledand in which correction is achieved with high accuracy, allowing alesion to be diagnosed accurately.

In this aspect, the image-correction unit may further raise theluminance value of the corrected fluorescence image to the power of thefirst exponent.

Configuring in this way, it is possible to reduce the dependency on thedistance by the image-correction unit, while maintaining adirect-proportionality relationship between the luminance value of thecorrected fluorescence image and the amount of the fluorescent agentpresent in the subject (i.e., the concentration of fluorescent agent).

A second aspect of the present invention is a fluoroscopy apparatuscomprising, an illumination portion having a light source that radiatesillumination light and excitation light onto a subject, afluorescence-imaging unit that acquires a fluorescence image by imagingfluorescence generated at the subject by the radiation of the excitationlight from the illumination portion, a return-light imaging unit thatacquires a reference image by imaging return light returning from thesubject by the radiation of the illumination light from the illuminationportion, and an image-correction unit that corrects the fluorescenceimage acquired by the fluorescence-imaging unit by using the referenceimage acquired by the return-light imaging unit, wherein in theimage-correction unit, a first exponent is obtained by a powerapproximation of a characteristic of luminance versus distance from theillumination portion to the subject, for the fluorescence image acquiredby the fluorescence-imaging unit when the excitation light of aprescribed luminance is radiated towards the subject; a second exponentis obtained by a power approximation of a characteristic of luminanceversus distance from the illumination portion to the subject, for areference image acquired by a return-light imaging unit when theillumination light of a prescribed intensity is radiated towards thesubject; a correction reference image is obtained by raising theluminance value of the reference image to the power of a third exponentthat is obtained by dividing the first exponent by the second exponent;a correction fluorescence image is obtained by dividing the fluorescenceimage by the correction reference image, or by raising the luminancevalue of the fluorescence image to the power of a fourth exponent thatis obtained by dividing the second exponent by the first exponent; and acorrected fluorescence image is obtained by dividing the correctionfluorescence image by the reference image.

According to this aspect, in the image-correction unit, it is sufficientto perform the power computation only once to correct the influence ofthe distance with high precision, and it is possible to obtain thecorrected fluorescence image in which the luminance value and the amountof the fluorescent agent present have a direct-proportionalityrelationship.

A third aspect of the present invention is a fluoroscopy apparatuscomprising, an illumination portion having a light source that radiatesillumination light and excitation light onto a subject, afluorescence-imaging unit that acquires a fluorescence image by imagingfluorescence generated at the subject by the radiation of the excitationlight from the illumination portion, a return-light imaging unit thatacquires a reference image by imaging return light returning from thesubject by the radiation of the illumination light from the illuminationportion, and an image-correction unit that corrects the fluorescenceimage acquired by the fluorescence-imaging unit by using the referenceimage acquired by the return-light imaging unit, wherein theimage-correction unit obtains a correction fluorescence image by raisinga luminance value of the fluorescence image to the power of the firstcorrection factor that is obtained such that ratios of a luminance ofthe fluorescence image, in which the luminance value of the fluorescenceimage has been raised to the power of a first correction factor, to aluminance of the reference image match each other at a plurality ofdifferent distances, and obtains a corrected fluorescence image bydividing the correction fluorescence image by the reference image.

According to this aspect, only the ratios of the intensities of theluminance of the fluorescence image and of the reference light image ata plurality of different distances need to be obtained, and it is notnecessary to obtain the distance information. In addition, because thedistance characteristic is not subjected to a power approximation, it ispossible to decide the first correction factor with a simplecomputation.

A fourth aspect of the present invention is a fluoroscopy apparatuscomprising, an illumination portion having a light source that radiatesillumination light and excitation light onto a subject, afluorescence-imaging unit that acquires a fluorescence image by imagingfluorescence generated at the subject by the radiation of the excitationlight from the illumination portion, a return-light imaging unit thatacquires a reference image by imaging return light returning from thesubject by the radiation of the illumination light from the illuminationportion, and an image-correction unit that corrects the fluorescenceimage acquired by the fluorescence-imaging unit by using the referenceimage acquired by the return-light imaging unit, wherein theimage-correction unit obtains the correction reference image by raisinga luminance value of the reference image to the power of the secondcorrection factor that is obtained such that ratios of a luminance ofthe fluorescence image to a luminance of the reference image, in whichthe luminance value of the reference image has been raised to the powerof a second correction factor, match each other at a plurality ofdifferent distances, and obtains a corrected fluorescence image bydividing the fluorescence image by the correction reference image.

According to this aspect, by deciding only the second correction factorfrom the luminance information of the fluorescence image and thereference image at a plurality of different distances, it is possible toeasily obtain the corrected fluorescence image having highquantitativeness, in which the distance dependencies of the fluorescenceimage and the reference image are reduced.

A fifth aspect of the present invention is a fluoroscopy apparatuscomprising, an illumination portion having a light source that radiatesillumination light and excitation light onto a subject, afluorescence-imaging unit that acquires a fluorescence image by imagingfluorescence generated at the subject by the radiation of the excitationlight from the illumination portion, a return-light imaging unit thatacquires a reference image by imaging return light returning from thesubject by the radiation of the illumination light from the illuminationportion, and an image-correction unit that corrects the fluorescenceimage acquired by the fluorescence-imaging unit by using the referenceimage acquired by the return-light imaging unit, wherein theimage-correction unit obtains a correction fluorescence image by raisinga luminance value of the fluorescence image to the power of the firstcorrection factor that is obtained such that ratios of a luminance ofthe fluorescence image, in which the luminance value of the fluorescenceimage has been raised to the power of a first correction factor, to aluminance of the reference image, in which the luminance value of thereference image has been raised to the power of a second correctionfactor, match each other at a plurality of different distances, obtainsthe correction reference image by raising the luminance value of thereference image to the power of the second correction factor, andobtains a corrected fluorescence image by dividing the correctionfluorescence image by the correction reference image.

According to this aspect, by deciding only two correction factors fromthe luminance information of the fluorescence image and the referenceimage at a plurality of different distances, it is possible to easilyobtain a corrected fluorescence image having high quantitativeness inwhich the distance dependencies of the fluorescence image and thereference image are reduced.

In the above-described aspect, an image-acquisition condition adjustingportion that adjusts an image acquisition condition on the basis of theluminance value of the fluorescence image acquired by thefluorescence-imaging unit, may be provided, wherein the image-correctionunit may normalize the luminance of the fluorescence image by the imageacquisition condition.

Configuring in this way, it is possible to obtain a fluorescence imagehaving suitable brightness with the image-acquisition conditionadjusting portion regardless of the luminance of the fluorescencegenerated at the subject. In this case, by normalizing the luminance ofthe fluorescence image by the image acquisition condition with theimage-correction unit, it is possible to standardize the luminance valueof the fluorescence image even when the image acquisition condition ofthe image-acquisition condition adjusting portion is changed.

In the above-described aspect, the image-acquisition condition adjustingportion may adjust exposure time of the fluorescence-imaging unit, andthe image-correction unit may divide the luminance value of thefluorescence image by the exposure time.

Configuring in this way, it is possible to adjust the brightness of thefluorescence image by using the image-acquisition condition adjustingportion by changing the exposure time of the fluorescence-imaging unit.In addition, even if the exposure time of the fluorescence-imaging unitis changed, it is possible to standardize the fluorescence image at aluminance value per unit time with the image-correction unit.

In the above-described aspect, the image-acquisition condition adjustingportion may adjust a gain factor of the fluorescence-imaging unit, andthe image-correction unit may divide the luminance value of thefluorescence image by the gain factor.

Configuring in this way, it is possible to adjust the brightness of thefluorescence image by using the image-acquisition condition adjustingportion by changing the gain factor of the fluorescence-imaging unit. Inaddition, even if the gain factor of the fluorescence-imaging unit ischanged, it is possible to standardize the fluorescence image at acertain luminance value per multiplication value with theimage-correction unit.

In the above-described aspect, the image-acquisition condition adjustingportion may adjust excitation-light intensity from the illuminationportion, and the image-correction unit may divide the luminance value ofthe fluorescence image by the excitation-light intensity.

Configuring in this way, it is possible to adjust the brightness of thefluorescence image by using the image-acquisition condition adjustingportion by changing the intensity of the excitation light radiated onthe subject. In addition, even if the excitation-light intensity fromthe illumination portion is changed, it is possible to standardize thefluorescence image at a certain luminance value per excitation-lightintensity with the image-correction unit.

In the above-described aspect, an image-acquisition condition adjustingportion that adjusts the image acquisition condition on the basis of theluminance value of the reference image acquired by the return-lightimaging unit is provided, wherein the image-correction unit maynormalize the luminance of the reference image by the image acquisitioncondition.

Configuring in this way, it is possible to obtain a reference imagehaving suitable brightness by using the image-acquisition conditionadjusting portion regardless of the luminance of the return lightreturning from the subject. In this case, by normalizing the luminanceof the reference image by the image acquisition condition with theimage-correction unit, even when the image acquisition condition of theimage-acquisition condition adjusting portion is changed, it is possibleto standardize the luminance value of the reference image.

In the above-described aspect, the image-acquisition condition adjustingportion may adjust exposure time of the return-light imaging unit, andthe image-correction unit divides the luminance value of the referenceimage by the exposure time.

Configuring in this way, it is possible to adjust the brightness of thereference image by changing the exposure time of the return-lightimaging unit with the image-acquisition condition adjusting portion. Inaddition, even if the exposure time of the return-light imaging unit ischanged, it is possible to standardize the reference image at aluminance value per unit time with the image-correction unit.

In the above-described aspect, the image-acquisition condition adjustingportion may adjust a gain factor of the return-light imaging unit, andthe image-correction unit may divide the luminance value of thereference image by the gain factor.

Configuring in this way, it is possible to adjust the brightness of thereference image by changing the gain factor of the return-light imagingunit with the image-acquisition condition adjusting portion. Inaddition, even if the gain factor of the return-light imaging unit ischanged, it is possible to standardize the reference image at a certainluminance value per multiplication value with the image-correction unit.

In the above-described aspect, the image-acquisition condition adjustingportion adjusts illumination light intensity from the illuminationportion, and the image-correction unit divides the luminance value ofthe reference image by the illumination light intensity.

Configuring in this way, it is possible to adjust the brightness of thereference image by using the image-acquisition condition adjustingportion by changing the intensity of the return light returning from thesubject. In addition, even if the illumination light intensity from theillumination portion is changed, it is possible to standardize thereference image at a certain luminance value per unit of illuminationlight intensity with the image-correction unit.

A sixth aspect of the present invention is a fluoroscopy systemcomprising a fluoroscopy apparatus according to the above-mentionedpresent invention and a calibration device that calibrates thefluoroscopy apparatus, wherein the calibration device is provided with astandard specimen and an observation-state setting mechanism thatchangeably sets an observation distance of the fluoroscopy apparatusrelative to the standard specimen, and wherein the fluoroscopy apparatusor the calibration device is provided with an exponent calculating unitthat calculates the first exponent and the second exponent on the basisof the observation distance set by the observation-state settingmechanism and the fluorescence image and the reference image acquired byimaging the standard specimen with the fluoroscopy apparatus.

According to this aspect, by calibrating the fluoroscopy apparatus withthe calibration device prior to the fluorescence observation, it ispossible to calculate the first exponent and the second exponent in thefluoroscopy apparatus more precisely by the operation of the exponentcalculating unit on the basis of the image acquired using the standardspecimen.

A seventh aspect of the present invention is a fluoroscopy systemcomprising a fluoroscopy apparatus according to the above-mentionedpresent invention and a calibration device that calibrates thefluoroscopy apparatus, wherein the calibration device is provided with astandard specimen and an observation-state setting mechanism thatchangeably sets an observation distance of the fluoroscopy apparatusrelative to the standard specimen, and wherein the fluoroscopy apparatusor the calibration device is provided with a correction-factorcalculating unit that calculates the first correction factor and thesecond correction factor on the basis of the observation distance set bythe observation-state setting mechanism and the fluorescence image andthe reference image acquired by imaging the standard specimen with thefluoroscopy apparatus.

According to this aspect, by calibrating the fluoroscopy apparatus withthe calibration device prior to the fluorescence observation, it ispossible to calculate the first correction factor and the secondcorrection factor in the fluoroscopy apparatus more precisely by theoperation of the exponent calculating unit on the basis of the imageacquired using the standard specimen.

An eighth aspect of the present invention is a fluorescence-imageprocessing method for performing the following correction processing ona fluorescence image acquired by imaging fluorescence produced at asubject by radiating excitation light from an illumination portion ontothe subject by using a reference image acquired by imaging return lightreturning from the subject when the subject is irradiated withillumination light from the illumination portion:FL _(revised) =FL _(after) /RL _(after),where,

FL_(revised) is a luminance value of a fluorescence image aftercorrection,FL _(after) =A×FL _(before) ^(x),RL _(after) =B×RL _(before) ^(y),

FL_(before) and RL_(before) are luminance values of the acquiredfluorescence image and reference image,

A and B are constants,

x is a reciprocal of an exponent obtained by a power approximation of acharacteristic of luminance versus distance from the illuminationportion to the subject, for the fluorescence image obtained by radiatingexcitation light of a prescribed intensity onto the subject, and

y is a reciprocal of an exponent obtained by a power approximation of acharacteristic of luminance versus distance from the illuminationportion to the subject, for the reference image obtained by radiatingillumination light of a prescribed intensity onto the subject.

A ninth aspect of the present invention is a fluorescence-imageprocessing method for performing the following correction processing ona fluorescence image acquired by imaging fluorescence produced at asubject by radiating excitation light from an illumination portion ontothe subject by using a reference image acquired by imaging return lightreturning from the subject when the subject is irradiated withillumination light from the illumination portion:FL _(revised)=(FL _(after) /RL _(after))^(1/x),where,

FL_(revised) is a luminance value of a fluorescence image aftercorrection,FL _(after) =A×FL _(before) ^(x),RL _(after) =B×RL _(before) ^(y),

FL_(before) and RL_(before) are luminance values of the acquiredfluorescence image and reference image,

A and B are constants,

x is a reciprocal of an exponent obtained by a power approximation of acharacteristic of luminance versus distance from the illuminationportion to the subject, for the fluorescence image obtained by radiatingexcitation light of a prescribed intensity onto the subject, and

y is a reciprocal of an exponent obtained by a power approximation of acharacteristic of luminance versus distance from the illuminationportion to the subject, for the reference image obtained by radiatingillumination light of a prescribed intensity onto the subject.

A tenth aspect of the present invention is a fluorescence-imageprocessing method for performing the following correction processing ona fluorescence image acquired by imaging fluorescence produced at asubject by radiating excitation light from an illumination portion ontothe subject by using a reference image acquired by imaging return lightreturning from the subject when the subject is irradiated withillumination light from the illumination portion:FL _(revised) =FL _(before) /RL _(after),where,

FL_(revised) is a luminance value of a fluorescence image aftercorrection,RL _(after) =B×RL _(before) ^(y),

FL_(before) and RL_(before) are luminance values of the acquiredfluorescence image and reference image,

B is a constant;

y is a value obtained by dividing a first exponent obtained by a powerapproximation of a characteristic of luminance versus distance from theillumination portion to the subject, for the fluorescence image obtainedby radiating excitation light of a prescribed intensity onto thesubject, by a second exponent obtained by a power approximation of acharacteristic of luminance versus distance from the illuminationportion to the subject, for the reference image obtained by radiatingillumination light of a prescribed intensity onto the subject.

An eleventh aspect of the present invention is a fluorescence-imageprocessing method for performing the following correction processing ona fluorescence image acquired by imaging fluorescence produced at asubject by radiating excitation light from an illumination portion ontothe subject by using a reference image acquired by imaging return lightreturning from the subject when the subject is irradiated withillumination light from the illumination portion:FL _(revised) =FL _(after) /RL _(before),

where,

FL_(revised) is a luminance value of a fluorescence image aftercorrection,FL _(after) =B×FL _(before) ^(1/y),

FL_(before) and RL_(before) are luminance values of the acquiredfluorescence image and reference image,

B is a constant,

y is a value obtained by dividing a first exponent obtained by a powerapproximation of a characteristic of luminance versus distance from theillumination portion to the subject, for the fluorescence image obtainedby radiating excitation light of a prescribed intensity onto thesubject, by a second exponent obtained by a power approximation of acharacteristic of luminance versus distance from the illuminationportion to the subject, for the reference image obtained by radiatingillumination light of a prescribed intensity onto the subject.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 is a block diagram showing, in outline, the configuration of afluoroscopy apparatus according to a first embodiment of the presentinvention.

FIG. 2 is a diagram showing a state in which the observation distancebetween an insertion portion of the fluoroscopy apparatus in FIG. 1 anda standard specimen is changed.

FIG. 3 is a flowchart showing a method of calculating an exponent in thefluoroscopy apparatus in FIG. 1.

FIG. 4A is a diagram showing an image with observation distance D0, inthe case where the size of a region of interest is not changed.

FIG. 4B is a diagram showing an image with observation distance D1, inthe case where the size of a region of interest is not changed.

FIG. 4C is a diagram showing an image with observation distance D2, inthe case where the size of a region of interest is not changed.

FIG. 5A is a diagram showing an image with observation distance D0, inthe case where the size of a region of interest is changed.

FIG. 5B is a diagram showing an image with observation distance D1, inthe case where the size of a region of interest is changed.

FIG. 5C is a diagram showing an image with observation distance D2, inthe case where the size of a region of interest is changed.

FIG. 6 is a flowchart showing another method of calculating an exponentin the fluoroscopy apparatus according to the first embodiment of thepresent invention.

FIG. 7 is a diagram showing an example of a concentration conversiontable provided in an image-combining unit of the fluoroscopy apparatusin FIG. 1.

FIG. 8 is a flowchart of image processing in the image processing unitin FIG. 1.

FIG. 9A is a graph showing the relationship between the luminance valueof a corrected fluorescence image and the observation distance.

FIG. 9B is a graph showing, as a reference example, the relationshipbetween the luminance value of a corrected fluorescence image and theobservation distance.

FIG. 10 is a graph comparing the deviation of luminance values of afluorescence image subjected to power arithmetic processing and thedeviation of luminance values of a fluorescence image without powerarithmetic processing.

FIG. 11 is a block diagram showing, in outline, the configuration of afluoroscopy apparatus according to a first modification of the firstembodiment of the present invention.

FIG. 12 is a flowchart of image processing in an image processing unitof a fluoroscopy apparatus according to a second modification of thefirst embodiment of the present invention.

FIG. 13 is a graph showing the relationship between the luminance valuein a fluoroscopy apparatus according to a second modification of thefirst embodiment of the present invention and the amount of fluorescentagent present.

FIG. 14 is a graph showing the relationship between the luminance value,as a reference example, in the fluoroscopy apparatus in FIG. 13 and theamount of a fluorescent agent present.

FIG. 15 is a flowchart of image processing in an image processing unitof a fluoroscopy apparatus according to a third modification of thefirst embodiment of the present invention.

FIG. 16 is a diagram showing a state in which simultaneous observationof two identical standard specimens positioned at different observationdistances is performed with a fluoroscopy apparatus according to a fifthmodification of the first embodiment of the present invention.

FIG. 17A is a diagram showing the relationship between the luminancevalue of a fluorescence image obtained by the fluoroscopy apparatusaccording to the fifth modification of the first embodiment of thepresent invention and the observation distance.

FIG. 17B is a diagram showing the relationship between the luminancevalue of a reference image obtained by the fluoroscopy apparatusaccording to the fifth modification of the first embodiment of thepresent invention and the observation distance.

FIG. 18 is a diagram showing a state in which simultaneous observationof two regions of interest in a standard specimen at differentobservation distances is performed with a fluoroscopy apparatusaccording to an eighth modification of the first embodiment of thepresent invention.

FIG. 19 is a diagram showing a state in which simultaneous observationof three or more regions of interest in a standard specimen at differentobservation distances is performed with a fluoroscopy apparatusaccording to a ninth modification of the first embodiment of the presentinvention.

FIG. 20 is a diagram showing a state in which simultaneous observationof regions of interest, including a continuous change in distance, in astandard specimen is performed with a fluoroscopy apparatus according toa tenth modification of the first embodiment of the present invention.

FIG. 21 is a diagram showing a standard deviation of FL/RL^(a) in aregion of interest at every correction factor.

FIG. 22 is a block diagram showing, in outline, the configuration of afluoroscopy apparatus according to a second embodiment of the presentinvention.

FIG. 23 is a diagram showing an example of a gain conversion tableprovided in a fluorescence-image normalization portion of thefluoroscopy apparatus in FIG. 22.

FIG. 24 is a flowchart of image processing in the image processing unitin FIG. 22.

FIG. 25 is a block diagram showing, in outline, the configuration of afluoroscopy apparatus according to a third embodiment of the presentinvention.

FIG. 26 is a diagram showing an example of an excitation-light intensityconversion table provided in a fluorescence-image normalization portionof the fluoroscopy apparatus in FIG. 25.

FIG. 27 is a flowchart of image processing in the image processing unitin FIG. 25.

DESCRIPTION OF EMBODIMENTS

[First Embodiment]

A fluoroscopy system, a fluoroscopy apparatus, and a fluorescence-imageprocessing method according to a first embodiment of the presentinvention will be described below with reference to the drawings.

As shown in FIG. 1, a fluoroscopy system 150 according to thisembodiment is provided with a fluoroscopy apparatus 101 and acalibration device 102 that is combined with the fluoroscopy apparatus101. The fluoroscopy apparatus 101 is an endoscope apparatus and isprovided with an elongated insertion portion 2 that is inserted inside abody cavity, an illumination unit (illumination portion) 20 thatincludes a light source 10 that emits illumination light from an end 2 aof the insertion portion 2, an image-acquisition unit 30 that isdisposed in the insertion portion 2 and acquires image information of anobservation target site X, which is the subject, an image processingunit 50 that performs arithmetic processing of the image informationacquired by the image-acquisition unit 30, and a monitor 4 that displaysthe images etc. that are processed by the image processing unit 50.

The light source 10 is provided with a xenon lamp 12 that emitsillumination light, a filter 14 that extracts the white light(illumination light) containing the excitation light from theillumination light emitted from the xenon lamp 12, and a coupling lens16 that focuses the white light containing the excitation lightextracted by the filter 14. The filter 14 extracts, for example, thewhite light containing the excitation light in a wavelength band between400 and 750 nm.

The illumination unit 20 is provided with a light guide fiber 22 that isdisposed along a longitudinal direction of the insertion portion 2 overnearly the entire length thereof and that guides the white lightcontaining the excitation light focused by a coupling lens 16 to the end2 a of the insertion portion 2, and a spreading lens 24 that is disposedon the end 2 a of the insertion portion 2 and that spreads the whitelight containing the excitation light guided by the light guide fiber 22to irradiate the observation target site X.

The image-acquisition unit 30 is provided with an objective lens 32 thatcollects return light returning from the observation target site Xirradiated with the white light containing the excitation light by theillumination unit 20 and a dichroic mirror 34 that reflects light of theexcitation wavelength or higher (the excitation light and fluorescence)in the return light collected by the objective lens 32, and thattransmits white light having a wavelength shorter than the excitationwavelength. The objective lens 32 and the spreading lens 24 are arrangedside-by-side on the end 2 a of the insertion portion 2.

This image-acquisition unit 30 is provided with an excitation-light cutfilter 36 that blocks the excitation light in the excitation light andfluorescence reflected by the dichroic mirror 34 and that transmits onlythe fluorescence (for example, near-infrared fluorescence), two focusinglenses 38 that respectively focus the fluorescence transmitted throughthis excitation-light cut filter 36 and the white light transmittedthrough the dichroic mirror 34, a fluorescence-imaging unit 42 thatimages the fluorescence focused by the focusing lenses 38 to obtain thefluorescence image information, and a white-light-imaging unit(return-light imaging unit) 44 that images the white light focused bythe focusing lenses 38 to obtain the reference image information.

The excitation-light cut filter 36 only transmits, for example,fluorescence in the wavelength band between 765 and 850 nm.

The fluorescence-imaging unit 42 is, for example, a high-sensitivitymonochrome CCD for fluorescence. The white-light-imaging unit 44 is, forexample, a color CCD for white light and is provided with a mosaicfilter (not shown).

The image processing unit 50 is provided with a fluorescenceexposure-time adjusting portion (image-acquisition condition adjustingportion) 54 that adjusts the exposure time (image acquisition condition)of the fluorescence-imaging unit 42 and a fluorescence-image generatingunit 52 that generates a two-dimensional fluorescence image on the basisof the fluorescence image information acquired by thefluorescence-imaging unit 42, a white-light exposure-time adjusting unit(image-acquisition condition adjusting portion) 58 that adjusts theexposure time (image acquisition condition) of the white-light-imagingunit 44 and a reference-image generating unit 56 that generates atwo-dimensional reference image on the basis of the reference imageinformation acquired by the white-light-imaging unit 44, and animage-correction unit 60 that corrects the fluorescence image generatedby the fluorescence-image generating unit 52 using the reference imagegenerated by the reference-image generating unit 56.

The fluorescence exposure-time adjusting portion 54 adjusts the exposuretime of the fluorescence-imaging unit 42 on the basis of the luminancevalues of the fluorescence image generated by the fluorescence-imagegenerating unit 52.

Similarly, the white-light exposure-time adjusting unit 58 adjusts theexposure time of the white-light-imaging unit 44 on the basis of theluminance values of the reference image generated by the reference-imagegenerating unit 56.

The image-correction unit 60 is provided with a fluorescence-imagenormalization portion 62 that normalizes the luminance of thefluorescence image generated by the fluorescence-image generating unit52 and a fluorescence-image preprocessing section 64 that performsarithmetic processing on the fluorescence image whose luminance isnormalized; a reference-image normalization portion 66 that normalizesthe luminance of the reference image obtained by the reference-imagegenerating unit 56 and a reference-image preprocessing section 68 thatperforms arithmetic processing on the reference image whose luminance isnormalized; and a division processing unit 72 that obtains a correctedfluorescence image K by dividing the correction fluorescence imageobtained by the fluorescence-image preprocessing section 64 by thecorrection reference image obtained by the reference-image preprocessingsection 68.

The fluorescence-image normalization portion 62 reads out the luminancevalue of the fluorescence image from the fluorescence-image generatingunit 52 and divides it by the exposure time of the fluorescence-imagingunit 42 set by the fluorescence exposure-time adjusting portion 54.

The fluorescence-image preprocessing section 64 obtains the correctionfluorescence image by raising the normalized luminance value of thefluorescence image to the power of the reciprocal 1/α (or −1/α) of afirst exponent α that is obtained by a power approximation of a distancecharacteristic of luminance versus observation distance Dn for thefluorescence image, which is obtained by the fluorescence-imaging unit42 by radiating the excitation light of a prescribed intensity onto theobservation target site X and which is normalized by thefluorescence-image normalization portion 62. Specifically, the powercomputation shown below is performed:FL _(after) =A×FL _(before) ^(x)  (1)

Here, FL_(after) is a luminance value of the correction fluorescenceimage, FL_(before) is a luminance value of the fluorescence image, x is1/α or −1/α, α is a first exponent, and A is a constant.

By performing this power computation, the correction fluorescence imagewhose luminance is proportional to (with −1/α, inversely proportionalto) the variation of the distance is obtained.

Similarly, the reference-image normalization portion 66 reads out theluminance information of the reference image from the reference-imagegenerating unit 56 and divides it by the exposure time of thewhite-light-imaging unit 44 set by the white-light exposure-timeadjusting unit 58.

In addition, the reference-image preprocessing section 68 obtains thecorrection reference image by raising the normalized luminance value ofthe reference image to the power of reciprocal 1/β(or −1/β) of a secondexponent β that is obtained by a power approximation of a distancecharacteristic of luminance versus observation distance Dn for thereference image, which is obtained by the white-light-imaging unit 44 byradiating the white light of a prescribed intensity onto the observationtarget site X and which is normalized by the reference-imagenormalization portion 66. Specifically, the power computation shownbelow is performed:RL _(after) =B×RL _(before) ^(y)  (2)

Here RL_(after) is a luminance value of the correction reference image,RL_(before) is a luminance value of the reference image, y is 1/β or−1/β, β is a second exponent, and B is a constant.

By performing this power computation, the correction reference imagewhose luminance is proportional to (with −1/β, inversely proportionalto) the variation of the distance is obtained.

In this case, based on a determination made prior to the fluorescenceobservation, the first exponent α and the second exponent β are decided,as described below, by, as shown in FIG. 2, disposing a standardspecimen 81 so as to oppose the end 2 a of the insertion portion 2, andusing the calibration device 102.

The calibration device 102 is provided with a translation stage(observation-state setting mechanism) 92 that changes the distance Dn(hereinafter referred to as “observation distance”) between the end 2 aof the insertion portion 2 and the standard specimen 81, a stagecontroller 94 that controls the position of the translation stage 92, adistance-information detector 96 that detects the distance informationof the observation distance Dn, and a dependency-constant determiningunit (exponent calculating unit) 98 that calculates the first exponent αand the second exponent β.

The dependency-constant determining unit 98 calculates the firstexponent α and the second exponent β on the basis of the normalizedfluorescence image and reference image sent from the fluorescence-imagenormalization portion 62 and the reference-image normalization portion66, respectively, and on the basis of the distance information detectedby the distance-information detector 96.

As the standard specimen 81, for example, one having an opticalcharacteristic close to that of a living body, such as tissue from a piglarge intestine, injected with fluorescent dye is desirable.

The method of calculating the first exponent α and the second exponent βin the dependency-constant determining unit 98 will be described belowwith reference to a flowchart in FIG. 3.

The observation distance Dn is first set by operating the stagecontroller 94 (step SC1), and the observation distance Dn at this timeis detected by the distance-information detector 96 and sent to thedependency-constant determining unit 98. In this state, the white lightcontaining the excitation light is radiated onto the standard specimen81 from the illumination unit 20. Then, the fluorescence and the whitelight are captured respectively with the fluorescence-imaging unit 42and the white-light-imaging unit 44, and the fluorescence image and thereference image are obtained by the fluorescence-image generating unit52 and the reference-image generating unit 56 (step SC2).

Next, the average values of the luminance values of regions that aredetermined in advance (hereinafter referred to as “regions of interest”)of the acquired fluorescence image and reference image are calculated(step SC3).

The method of obtaining the luminance values is explained with thefollowing reference example as an illustration.

For example, as shown in FIG. 2, the illumination light is radiated ontothe standard specimen 81 while changing the observation distance Dn toD0, D1, and D2 (D0<D1<D2) to obtain the fluorescence images such asthose shown in FIGS. 4A to 4C and FIGS. 5A to 5C. In FIG. 2, referencesign 83 is a field of view of the fluorescence-imaging unit 42 andreference sign 85 is a region of interest.

If the fluorescence intensity in the standard specimen 81 is constant,in other words, for example, if the surface of the standard specimen 81,which is the subject, is substantially flat, as shown in FIGS. 4A to 4C,the luminance value is calculated by making the size of the region ofinterest 85 constant regardless of the observation distance Dn. On theother hand, if the fluorescence intensity in the standard specimen 81 isnot constant, in other word, for example, if there are irregularities onthe surface of the standard specimen 81 and if there are nonuniformitiesin the fluorescence distribution in the standard specimen 81, as shownin FIGS. 5A to 5C, the luminance value is calculated by changing thesize of the region of interest 85 in accordance with the observationdistance Dn. By changing the size of the region of interest 85, it ispossible to obtain the luminance value of the same site even when theobservation distance Dn is changed.

Next, the average values of the luminance values in the regions ofinterest, which are calculated from the fluorescence image and referenceimage, are divided by the exposure time and normalized by thefluorescence-image normalization portion 62 and the reference-imagenormalization portion 66 (step SC4), respectively, and thereafter, theyare sent to the dependency-constant determining unit 98, and theluminance values are plotted in association with the distanceinformation (step SC5).

The stage controller 94 repeats the above-described steps SC1 to SC6multiple times for a predetermined number of times a (a is at least twoor more) (step SC6). For example, the observation distance Dn is changedto D0 and D1, for example, a regression curve is obtained by a powerapproximation of the obtained distance characteristics, in other words,by performing regression to power functions D^(α) and D^(β) (step SC7),and thereby, the first exponent α and the second exponent β thatindicate the dependencies on the observation distance Dn are calculated(step SC8). The results of the determination of the first exponent α andthe second exponent β from the regression curve, as the referenceexamples, are shown in FIGS. 17A and 17B. In FIGS. 17A and 17B, thevertical axis indicates the luminance value in the fluorescence image orthe reference image and the horizontal axis indicates the observationdistance Dn.

By doing so, it is possible to determine the observation distance Dn andcorresponding accurate exponents for the fluorescence image and thereference image with the dependency-constant determining unit 98. Thefirst exponent α and the second exponent β determined by thedependency-constant determining unit 98 are sent to thefluorescence-image preprocessing section 64 and the reference-imagepreprocessing section 66, respectively.

In this embodiment, the distance-information detector 96 may be omitted,and distance information of the observation distance Dn may be input tothe dependency-constant determining unit 98 manually.

In addition, in this embodiment, although the average values of theluminance values of the regions of interest in the fluorescence imageand the reference image are calculated before the normalization (seestep SC3 in FIG. 3), and thereafter, the average values are normalizedby treating them as the luminance values and dividing them by theexposure time (see SC4 in FIG. 3), instead of this, as shown in theflowchart in FIG. 6, for example, the normalization may be performed bydividing the luminance of the whole fluorescence image and the luminanceof the whole reference image by the exposure time, respectively (stepSC3′), and thereafter, the average values of the normalized luminancevalues of the regions of interest in the fluorescence image and thereference image may be calculated (step SC4′).

In addition, the image processing unit 50 is provided with animage-combining unit 74 that generates an image by combining thereference image S generated by the reference-image generating unit 56and the corrected fluorescence image K generated by an image-correctionunit 75. The image-combining unit 74 combines the corrected fluorescenceimage K obtained by the division processing unit 72 and the referenceimage S generated by the reference-image generating unit 56 such thatthe combined images are arranged in parallel and simultaneouslydisplayed on the monitor 4. In addition, as shown in FIG. 7, theimage-combining unit 74 has a concentration conversion table 87 in whichthe luminance values of the corrected fluorescence image K and theamount of fluorescent agent present (in other words, the concentrationof fluorescent agent) are associated with each other, which allows thefluorescence concentration in a specific region to be displayed on themonitor 4.

The operation of the thus-configured fluoroscopy apparatus 101 andfluorescence-image processing method according to this embodiment willbe described.

In order to perform observation of, for example, an observation targetsite X in a body cavity of a living body using the fluoroscopy apparatus101 according to this embodiment, the insertion portion 2 is insertedinto the body cavity, and the end 2 a is directed so as to oppose theobservation target site X.

In this state, the illumination unit 20 is operated, and the white lightcontaining the excitation light, which is emitted from the xenon lamp 12and extracted by the filter 14, is focused by the coupling lens 16 so asto enter the light guide fiber 22. The white light containing theexcitation light that has entered the light guide fiber 22 is guided tothe end 2 a of the insertion portion 2, is spread by the spreading lens24, and is radiated onto the observation target site X.

In the observation target site X, the fluorescent agent containedtherein is excited by the excitation light, emitting fluorescence, andthe white light is reflected at the surface of the observation targetsite X. The fluorescence and the return light from the white light arecollected by the objective lens 32 of the insertion portion 2 and aresplit into different wavelengths by the dichroic mirror 34.

At the dichroic mirror 34, the light of the excitation wavelength orhigher, in other words, the excitation light, and fluorescence arereflected, and the white light having a shorter wavelength than theexcitation wavelength is transmitted.

The excitation light among the excitation light and fluorescencereflected at the dichroic mirror 34 is removed by the excitation-lightcut filter 36, and only the fluorescence is focused by the focusing lens38. The fluorescence is captured by the fluorescence-imaging unit 42 andis obtained as the fluorescence image information.

In addition, the white light transmitted through the dichroic mirror 34is focused by the focusing lens 38, is captured by thewhite-light-imaging unit 44, and is obtained as the reference imageinformation.

Either fluorescence image information or the reference image informationcan be obtained before the other, or both can be obtainedsimultaneously.

The fluorescence image information obtained by the fluorescence-imagingunit 42 and the reference image information obtained by thewhite-light-imaging unit 44 are individually input to the imageprocessing unit 50 and subjected to image processing. The imageprocessing in the image processing unit 50 will be described below withreference to a flowchart in FIG. 8.

In the image processing unit 50, the fluorescence image information isinput to the fluorescence-image generating unit 52, where atwo-dimensional fluorescence image is generated. In this case, theexposure time of the fluorescence-imaging unit 42 is set by thefluorescence exposure-time adjusting portion 54 on the basis of theluminance value of the fluorescence image generated by thefluorescence-image generating unit 52 (step SF1). By doing so, afluorescence image having suitable brightness is obtained by thefluorescence-image generating unit 52 regardless of the luminance of thefluorescence emitted from the observation target site X (step SF2).

Similarly, the reference image information is input to thereference-image generating unit 56, where a two-dimensional referenceimage is generated. In this case, the exposure time of thewhite-light-imaging unit 44 is adjusted by the white-light exposure-timeadjusting unit 58 on the basis of the luminance value of the referenceimage generated by the reference-image generating unit 56 (step SR1). Bydoing so, a reference image having suitable brightness is obtained bythe reference-image generating unit 56 regardless of the luminance ofthe white light returned from the observation target site X (step SR2).

The fluorescence image generated by the fluorescence-image generatingunit 52 and the reference image generated by the reference-imagegenerating unit 56 are individually sent to the image-correction unit60.

In the image-correction unit 60, first, the fluorescence-imagenormalization portion 62 divides the luminance value of the fluorescenceimage by the exposure time of the fluorescence-imaging unit 42 (stepSF3). By doing so, the differences in the exposure time in thefluorescence image are normalized, and the fluorescence image isstandardized at luminance value per unit time. In addition, thereference-image normalization portion 66 divides the luminance value ofthe reference image by the exposure time of the white-light-imaging unit44 (step SR3). By doing so, the differences in the exposure time in thereference image are normalized, and the reference image is standardizedat luminance value per unit time.

The fluorescence image whose luminance has been normalized by thefluorescence-image normalization portion 62 is sent to thefluorescence-image preprocessing section 64, and the reference imagewhose luminance has been normalized by the reference-image normalizationportion 66 is sent to the reference-image preprocessing section 68.

Next, in the fluorescence-image preprocessing section 64, in accordancewith the above-mentioned correction arithmetic expression (1), theluminance value of each pixel in the fluorescence image is raised to thepower of the reciprocal 1/α of the first exponent α (step SF4). By doingso, information related to the power of the distance is cancelled, and acorrection fluorescence image in which the luminance is proportional tothe variation of the distance is obtained. In addition, in thereference-image preprocessing section 68, in accordance with theabove-mentioned correction arithmetic expression (2), the luminancevalue of each pixel in the reference image is raised to the power of thereciprocal 1/β of the second exponent β (step SR4). By doing so,information related to the power of the distance is cancelled, and acorrection reference image in which the luminance is proportional to thevariation of the distance is obtained.

The correction fluorescence image and the correction reference image areindividually sent to the division processing unit 72, where thecorrection fluorescence image is divided by the correction referenceimage (step SFR5). Since the correction fluorescence image and thecorrection reference image are related to each other such that theluminance is proportional to the variations of the distances byperforming the above-mentioned power arithmetic processing, as shown inFIG. 9A, by dividing the correction fluorescence image by the correctionreference image, it is possible to obtain a corrected fluorescence imageK having quantitativeness, in which the dependencies on distance arecancelled, and the correction is achieved with a high accuracy.

The corrected fluorescence image K and the correction reference imageobtained in the division processing unit 72 are sent to theimage-combining unit 74. In the image-combining unit 74, the correctedfluorescence image K and the reference image S are combined anddisplayed on the monitor 4 simultaneously, and on the basis of theconcentration conversion table 87, the fluorescence concentration in aspecific region is displayed on the monitor 4.

As described above, according to the fluoroscopy apparatus 101 andfluorescence-image processing method of this embodiment, by subjectingthe fluorescence image to the correction processing after processing theinformation related to the power of the distance contained in thefluorescence image and the reference image, it is possible to performobservation by obtaining the corrected fluorescence image K having highquantitativeness, in which the dependencies on distance of thefluorescence image and the reference image are cancelled. By doing so,it is possible to diagnose a lesion accurately from the luminance valuesof the corrected fluorescence image K.

As a reference example, the relationship between the luminance value ofthe fluorescence image and the observation distance Dn when thefluorescence image is divided by the reference image without performingpower arithmetic processing is shown in FIG. 9B. Since each of thefluorescence image and the reference image that is not subjected topower arithmetic processing contains the information related to thepower of the distance, the dependencies on the distance cannot becompletely cancelled by a simple division of the fluorescence image bythe reference image, and the influence of distance remains in thedivided fluorescence image. FIG. 10 shows the relationship between theobservation distance Dn and the deviations from the average values ofthe luminance values of the fluorescence image with/without the powercomputation. In FIG. 10, the vertical axis indicates the deviation (%)from the average value of the luminance value and the horizontal axisindicates the observation distance Dn.

In addition, in this embodiment, although a correction factor for thefluorescence-image preprocessing section 64 is illustrated as x=1/α anda correction factor for the reference-image preprocessing section 68 isillustrated as y=1/β, correction factors obtained by respectivelymultiplying x and y by a constant k may be used. Similar effects canalso be achieved in this case.

In addition, if α or β is chosen for the value of the constant k, it ispossible to make the correction factor of either the fluorescence-imagepreprocessing section 64 or the reference-image preprocessing section 68equal to unity, thereby reducing the amount of calculation.

This embodiment can be modified as follows.

For example, as a first modification, as shown in FIG. 11, theconfiguration may include the fluoroscopy apparatus 100 only and mayomit the calibration device. In such a case, the preset correctionfactor x is stored in the fluorescence-image preprocessing section 64,and a preset correction factor y is stored in the reference-imagepreprocessing section 66.

In a second modification, for example, as shown in a flowchart in FIG.12, in the image-correction unit 60, a postprocessing section (notshown) may be provided between the division processing unit 72 and theimage-combining unit 74, and the postprocessing section may furtherraise the luminance value of each pixel in the corrected fluorescenceimage K obtained by the division processing unit 72 to the power of thefirst exponent α (step SFR6). By doing so, as shown in FIG. 13, it ispossible to reduce the dependency on the distance by using thepostprocessing section while maintaining the proportional relationshipbetween the luminance value of the corrected fluorescence image K andthe amount of fluorescent agent present (i.e., the concentration offluorescent agent). As a reference example, FIG. 14 shows therelationship between the luminance value of the corrected fluorescenceimage K and the concentration of fluorescent agent when the luminancevalue is not raised to the power of the first exponent α by thepostprocessing section.

In this embodiment, although the image-correction unit 60 is providedwith the fluorescence-image preprocessing section 64, in a thirdmodification, for example, the fluorescence-image preprocessing section64 may be omitted, and the reference-image preprocessing section 68 mayobtain the correction reference image by raising the luminance value ofthe reference image to the power of a third exponent α/β (or −α/β) thatis obtained by dividing the first exponent α by the second exponent β.

In this case, as shown in a flowchart in FIG. 15, the fluorescence imagenormalized by the fluorescence-image normalization portion 62 may besent to the division processing unit 72, and the power computation asdescribed below may be performed by the reference-image preprocessingsection 68 (step SR4′):RL _(after) =B×RL _(before) ^(z)  (3)

Here, RL_(after) is a luminance value of the correction reference image,RL_(before) is a luminance value of the reference image, z is a thirdexponent (α/β or −α/β), α is a first exponent, β is a second exponent,and B is a constant.

By doing so, in the image-correction unit 60, it is sufficient toperform the power computation only once to correct the influence of thedistance with high precision, and it is possible to obtain the correctedfluorescence image K in which the luminance value and the amount of thefluorescent agent present are in a directly proportional relationship.

In this embodiment, although the image-correction unit 60 is providedwith the reference-image preprocessing section 66, in a fourthmodification, for example, the reference-image preprocessing section 66may be omitted, and the fluorescence-image preprocessing section 64 mayobtain the correction fluorescence image by raising the luminance valueof the fluorescence image to the power of a fourth exponent β/α (or−β/α) that is obtained by dividing the second exponent β by the firstexponent α, that is, the reciprocal of the third exponent α/β (or −α/β).

In this case, the reference image normalized by the reference-imagenormalization portion 66 may be sent to the division processing unit 72,and the power computation as described below may be performed by thefluorescence-image preprocessing section 64:FL _(after) =A×FL _(before) ^(z′)  (4)

Here, FL_(after) is a luminance value of the correction fluorescenceimage, FL_(before) is a luminance value of the fluorescence image, z′ isa fourth exponent β/α (or −β/α), α is a first exponent, β is a secondexponent, and A is a constant.

By doing so, in the image-correction unit 60, it is sufficient toperform the power computation only once to correct the influence of thedistance with high precision.

In the third modification, although the reference-image preprocessingsection 68 obtains the correction reference image by raising theluminance value of the reference image to the power of the thirdexponent α/β (or −α/β), serving as the correction factor z, in a fifthmodification, instead of the correction factor z, the correction factor(second correction factor) a, which is defined in the following methodmay be used in a dependency-constant determining unit (correction-factorcalculating unit) (not shown).

As shown in FIG. 16, when two identical standard specimens 81 arepositioned at different observation distances D0 and D1 within the rangeof the field of view of the fluorescence-imaging unit 42 and thewhite-light-imaging unit 44 and observed simultaneously, the correctionfactor a is set such that the luminance value obtained from the regionof interest 85 of the corrected fluorescence image positioned at theobservation distance D0 substantially matches the luminance valueobtained from the region of interest 85 of the corrected fluorescenceimage positioned at the observation distance D1.

Specifically, the correction factor a that is obtained in the followingarithmetic expression is calculated, in other words, the correctionfactor a is calculated such that the ratio of the fluorescence image tothe correction reference image in which the luminance value of thereference image of the standard specimen 81 positioned at theobservation distance D0 is raised to the power of the correction factora substantially matches the ratio of the fluorescence image to thecorrection reference image in which the luminance value of the referenceimage of the standard specimen 81 positioned at the observation distanceD1 is raised to the power of the correction factor a:FL(D0)/RL(D0)^(a) =FL(D1)/RL(D1)^(a)  (5)a=log(FL(D1)/FL(D0))/log(RL(D1)/RL(D0))  (6)

Here, FL(D0) is a luminance value of the fluorescence image at theobservation distance D0, RL(D0) is a luminance value of the referenceimage at the observation distance D0, FL(D1) is a luminance value of thefluorescence image at the observation distance D1, and RL(D1) is aluminance value of the reference image at the observation distance D1.

The reference-image preprocessing section 68 obtains the correctionreference image of the observation target site X in a body cavity of aliving body in accordance with the following arithmetic expression andsends it to the division processing unit 72:RL _(after) =B×RL _(before) ^(a)  (7)

According to expressions (5) and (6), the correction factor a iscalculated such that the luminance values at two locations at differentobservation distances (D0 and D1) in the corrected fluorescence image Kmatch each other. On the other hand, as shown in FIGS. 17(A) and 17(B),although the distance dependencies of the luminance value of thefluorescence image and of the luminance value of the reference imagediffer in the exponent, that is, the power of the distance, both are ina substantially inversely proportional relationship with respect to thepower of the distance. Therefore, the values of the correction factor adecided at two locations that differ in the observation distances becomeclose to the third exponent α/β, and it is possible to reduce thedifference in the distance dependencies even when correction using thecorrection factor a is performed on an image with an observationdistance other than the observation distances D0 and D1.

If the observation distances D0 and D1 are close to each other, becausethe differences between the luminance values of the fluorescence imagesand the luminance values of the reference images at respective distancesare small and errors tend to occur, it is preferred that the differencebetween the values of the observation distances D0 and D1 be as large aspossible.

It is not required to obtain a plurality of images by changing theobservation distance Dn to obtain exponents from power approximations,and even when the observation distances D0 and D1 are unknown, it ispossible to calculate a correction factor a and to set the correctionfactor a easily.

In the fourth modification, although the fluorescence-imagepreprocessing section 64 obtains the correction fluorescence image byraising the luminance value of the fluorescence image to the power ofthe reciprocal of the third exponent β/α (or −β/α), in a sixthmodification, the correction may be performed using the reciprocal(first correction factor) 1/a of the correction factor a calculated inthe fifth modification.

Specifically:FL _(after) =A×FL _(before) ^((1/a))  (8).

With this configuration, effects similar to those in the fifthmodification can be achieved.

In the fourth modification, although the correction factor a is set as acorrection value for the reference-image preprocessing section 64, suchthat the luminance values of the corrected fluorescence image in twoidentical standard specimens 81 at different observation distances Dnsubstantially match, in a seventh modification, correction factors(first correction factor and second correction factor) b and c obtainedin accordance with the following arithmetic expressions may be set asthe correction factors for the fluorescence-image preprocessing section64 and the reference-image preprocessing section 68, respectively:FL(D0)^(b) /RL(D0)^(c) =FL(D1)^(c) /RL(D1)^(c)  (9)c/b=log(FL(D1)/FL(D0))/log(RL(D1)/RL(D0))  (10).

In expression (10), although the ratio of b and c can be derived,numerical values cannot be decided. Thus, the value of c can be decidedin accordance with expression (10) by arbitrarily setting the value of b(for example 2). Instead of this, after the value of c is setarbitrarily, the value of b may be decided in accordance with expression(10).

The decided correction factor b is set in the fluorescence-imagepreprocessing section 64, and the fluorescence-image preprocessingsection 64 performs the following computation:FL _(after) =A×FL _(before) ^(b)  (11).

The decided correction factor c is set in the reference-imagepreprocessing section 68, and the reference-image preprocessing section68 performs the following computation:RL _(after) =B×RL _(before) ^(c)  (12)

The value obtained by dividing the correction factor c by the correctionfactor b is equal to the correction factor a calculated in the fourthmodification, and it also has a value close to that of the thirdexponent α/β. This modification also achieves effects equivalent tothose in the fourth modification.

In the fifth to seventh modifications, although two identical standardspecimens 81 are positioned at different observation distances D0 andD1, and the correction factors a are calculated from the luminancevalues obtained from the respective regions of interest 85, in an eighthmodification, as shown in FIG. 18, the standard specimen 81 may beplaced at an angle within the ranges of the fields of view of thefluorescence-imaging unit 42 and the white-light-imaging unit 44, andthe correction factors a may be calculated from the luminance valuesobtained from two regions of interest 85 located at differentobservation distances Dn on one standard specimen 81.

In this case, as in this embodiment, the correction factor a, and thecorrection factors b and c may be calculated such that the luminancevalue obtained in the region of interest 85 in the correctedfluorescence image at the observation distance D0 substantially matchesthe luminance value obtained in the region of interest 85 in thecorrected fluorescence image at the observation distance D1. By doingso, it is possible to set the correction factors a, b, and c easily byusing only one standard specimen 81.

In the fifth modification, although the correction factor a is set bythe luminance values obtained from two regions of interest 85 located atdifferent observation distances Dn, in a ninth modification, as shown inFIG. 19, the correction factor a may be calculated from the luminancevalues of two regions of interest 85 having observation distances Dnthat are close to each other among the luminance values obtained fromthree or more regions of interest 85 in the standard specimen 81 placedat an angle within the ranges of the fields of view of thefluorescence-imaging unit 42 and the white-light-imaging unit 44.

For example, a correction factor a01 in which the luminance valueobtained from the region of interest 85 at the observation distance D0substantially matches the luminance value obtained from the region ofinterest 85 at the observation distance D1 and a correction factor a02in which the luminance value obtained from the region of interest 85 atthe observation distance D1 substantially matches the luminance valueobtained from the region of interest 85 at the observation distance D2may be calculated, and the correction factor a may be derived from theaverage values (a=(a01+a02)/2) of each of the correction factors a01 anda02. By doing so, it is possible to reduce the errors caused in thecorrection factors a on the basis of the luminance values of a pluralityof regions of interest 85.

In a tenth modification, as shown in FIG. 20, with the standard specimen81 placed at an angle within the ranges of the fields of view of thefluorescence-imaging unit 42 and the white-light-imaging unit 44, aregion including a continuous distance change, for example, from theobservation distance D0 to the observation distance D1, may be set asthe region of interest 85, the correction factor a may be varied from 1in increments of 0.05 to calculate FL/RL^(a) for every pixel in theregion of interest 85, and, as shown in FIG. 21, the standard deviationσ of FL/RL^(a) in the region of interest 85 for every correction factora may be calculated, and thereby, the correction factor a that yieldsthe smallest standard deviation σ may be set. By doing so, the errorscaused in the correction factor a can be reduced.

[Second Embodiment]

Next, a fluoroscopy apparatus and fluorescence-image processing methodaccording to a second embodiment of the present invention will bedescribed.

The fluoroscopy apparatus 200 according to this embodiment differs fromthe first embodiment in that, as shown in FIG. 22, the image processingunit 250 is provided with, instead of the fluorescence exposure-timeadjusting portion 54, a fluorescence-gain-value adjusting portion(image-acquisition condition adjusting portion) 254 that adjusts a gainvalue (image acquisition condition, gain factor) that amplifies thefluorescence image information acquired by the fluorescence-imaging unit42.

In the following, parts having the same configuration as those in thefluoroscopy apparatuses 100 and 101 according to the first embodimentwill be assigned the same reference signs, and a description thereofwill be omitted.

The fluorescence-gain-value adjusting portion 254 adjusts the gain valueof the fluorescence-imaging unit 42 on the basis of the luminance valueof the fluorescence image generated by the fluorescence-image generatingunit 52.

The gain value of the fluorescence-imaging unit 42 that is set by thefluorescence-gain-value adjusting portion 254 is input to thefluorescence-image normalization portion 62. In addition, thefluorescence-image normalization portion 62 is provided with again-factor conversion table 287, like that shown in FIG. 23, in whichgain values and gain multiplication factors are associated with eachother.

With the thus-configured fluoroscopy apparatus 200, as shown in aflowchart in FIG. 24, the gain value of the fluorescence-imaging unit 42is set by the fluorescence-gain-value adjusting portion 254 on the basisof the luminance value of the fluorescence image generated by thefluorescence-image generating unit 52 (step SG1). By doing so, afluorescence image having suitable brightness is obtained by thefluorescence-image generating unit 52 regardless of the incident lightintensity of the fluorescence generated at the observation target site X(step SG2).

In the fluorescence-image normalization portion 62, the luminance valueof the fluorescence image read out from the fluorescence-imagegenerating unit 52 is divided by the gain multiplication factor thatcorresponds to the gain value at the time of acquisition of thefluorescence image by the fluorescence-imaging unit 42 (step SG3). Bydoing so, the influence of the gain value in the fluorescence image isnormalized, and the fluorescence image can be standardized at a certainluminance value per multiplication value.

[Third Embodiment]

Next, a fluoroscopy apparatus and a fluorescence-image processing methodaccording to a third embodiment of the present invention will bedescribed.

The fluoroscopy apparatus 300 according to this embodiment differs fromthe first embodiment in that, as shown in FIG. 25, the light source 310is further provided with a semiconductor laser 312, and the imageprocessing unit 350 is provided with, instead of the fluorescenceexposure-time adjusting portion 54 and the white-light exposure-timeadjusting unit 58, an excitation-light adjusting portion(image-acquisition condition adjusting portion) 354 that adjusts thelight-adjustment level of the excitation light emitted from theillumination unit 20 and a white-light adjusting portion(image-acquisition condition adjusting portion) 358 that adjusts thelight-adjustment level of the illumination light.

In the following, parts having the same configuration as those in thefluoroscopy apparatuses 100 and 101 according to the first embodimentwill be assigned the same reference signs, and a description thereofwill be omitted.

The light source 310 is provided with the xenon lamp 12, a xenon lampcontroller 13, an infrared-cut filter 314 that blocks infrared light inthe illumination light and transmits only the white light emitted fromthe xenon lamp 12, the semiconductor laser 312 that emits the excitationlight in the wavelength band of 740 nm, a semiconductor laser controller313, and a light source dichroic mirror 315 that transmits the whitelight transmitted through the infrared-cut filter 314 and that reflectsthe excitation light emitted from the semiconductor laser 312, therebyguiding the white light and the excitation light into the same opticalpath. The infrared-cut filter 314 transmits only, for example, the whitelight in the wavelength band between 400 and 680 nm. Reference sign 316Ais a first coupling lens that focuses the white light transmittedthrough the infrared-cut filter 314, and reference sign 316B is a secondcoupling lens that focuses the white light and the excitation light thatare guided into the same optical path by the light-source dichroicmirror 315.

The excitation-light adjusting portion 354 adjusts the light-adjustmentlevel of the semiconductor laser 312 with the semiconductor lasercontroller 313 on the basis of the luminance value of the fluorescenceimage generated by the fluorescence-image generating unit 52.

Similarly, the white-light adjusting portion 358 adjusts thelight-adjustment level of the xenon lamp 12 with the xenon lampcontroller 13 on the basis of the luminance value of the reference imagegenerated by the reference-image generating unit 56.

The light-adjustment level of the semiconductor laser controller 313that is set by the excitation-light adjusting portion 354 is input tothe fluorescence-image normalization portion 62. The fluorescence-imagenormalization portion 62 is provided with an excitation-light intensityconversion table 387, like that shown in FIG. 26, in which thelight-adjustment level and the excitation-light intensity are associatedwith each other.

Similarly, the light-adjustment level of the xenon lamp controller 13that is set by the white-light adjusting portion 358 is input to thereference-image normalization portion 66. The reference-imagenormalization portion 66 is provided with a white-light intensityconversion table (not shown) in which the light-adjustment level and thewhite-light intensity (illumination light intensity) are associated witheach other. The excitation-light intensity and the white-light intensitymay be decided by respective intensity ratios based on the minimumvalues.

With the thus-configured fluoroscopy apparatus 300, the white lightemitted from the xenon lamp 12, transmitted through the infrared-cutfilter 314, and focused by the first coupling lens 316A is transmittedthrough the light source dichroic mirror 315, and the excitation lightemitted from the semiconductor laser 312 is reflected at the lightsource dichroic mirror 315, and both the white light and the excitationlight are guided along the same optical path and are focused by a secondcoupling lens 316B so as to enter the light guide fiber 22.

In the image-correction unit 60, as shown in a flowchart in FIG. 27, thelight-adjustment level of the semiconductor laser controller 313 is setby the excitation-light adjusting portion 354 on the basis of theluminance value of the fluorescence image generated by thefluorescence-image generating unit 52 (step SL1). By doing so, in thefluorescence-image generating unit 52, a fluorescence image havingsuitable brightness is obtained by varying the intensity of thefluorescence generated at the observation target site X (step SL2).

Similarly, the light-adjustment level of the xenon lamp controller 13 isset by the white-light adjusting portion 358 on the basis of theluminance value of the reference image generated by the reference-imagegenerating unit 56 (step SM1). By doing so, in the reference-imagegenerating unit 56, a reference image having suitable brightness isobtained by varying the intensity of the white light returning from theobservation target site X (step SM2).

Then, the fluorescence-image normalization portion 62 performs divisionof the luminance value of the fluorescence image read out from thefluorescence-image generating unit 52 by the excitation-light intensitycorresponding to the light-adjustment level of the semiconductor lasercontroller 313 (step SL3). By doing so, the influence of thelight-adjustment level of the excitation light is normalized, and thefluorescence image can be standardized at a certain luminance value perunit of excitation-light intensity.

In addition, the reference-image normalization portion 66 divides theluminance value of the reference image read out from the reference-imagegenerating unit 56 by the white-light intensity corresponding to thelight-adjustment level of the xenon lamp controller 13 (step SM3). Bydoing so, the influence of the light-adjustment level of theillumination light is normalized, and the reference image can bestandardized at a certain luminance value per unit of white-lightintensity.

Although the embodiments of the present invention have been describedabove with reference to the drawings, the specific configurations arenot limited to these embodiments, and design alterations and the likewithin a range that does not depart from the spirit of the presentinvention are encompassed. For example, the present invention is notlimited to aspects that are employed in the above-described embodimentsand modifications thereof; without particular limitation, it may also beapplied to embodiments formed by appropriately combining theseembodiments and modifications thereof.

In addition, each of the above-mentioned embodiments has been describedin terms of examples where near-infrared fluorescence and white lightare used. However, the present invention is not limited thereto and, forexample, fluorescence having visible wavelengths may be used in place ofthe near-infrared fluorescence, or excitation light having visiblewavelengths may be used in place of the white light.

In addition, for example, in the fluorescence-image preprocessingsection 64 and the reference-image preprocessing section 68, the powercomputation may be performed after noise components in thefluorescence-imaging unit 42 and the white-light-imaging unit 44 havebeen subtracted. By doing so, the precision of the power computation canbe improved.

{Reference Signs List}

-   10, 310 light source-   20 illumination unit (illumination portion)-   42 fluorescence-imaging unit-   44 white-light-imaging unit (return-light imaging unit)-   54 fluorescence exposure-time adjusting portion (image-acquisition    condition adjusting portion)-   58 white-light exposure-time adjusting unit (image-acquisition    condition adjusting portion)-   60, 460 image-correction unit-   92 translation stage (observation-state setting mechanism)-   98 dependency-constant determining unit (exponent calculating unit,    correction-factor calculating unit)-   100, 101, 200, 300, 400 fluoroscopy apparatus-   102 calibration device-   150 fluoroscopy system-   254 fluorescence-gain-value adjusting portion (image-acquisition    condition adjusting portion)-   354 excitation-light adjusting portion (image-acquisition condition    adjusting portion)-   358 white-light adjusting portion (image-acquisition condition    adjusting portion)

The invention claimed is:
 1. A fluoroscopy apparatus comprising: anillumination portion having a light source that radiates illuminationlight and excitation light onto a subject; a fluorescence-imaging unitthat acquires a fluorescence image by imaging fluorescence generated atthe subject by the radiation of the excitation light from theillumination portion; a return-light imaging unit that acquires areference image by imaging return light returning from the subject bythe radiation of the illumination light from the illumination portion;and an image-correction unit that corrects the fluorescence imageacquired by the fluorescence-imaging unit by using the reference imageacquired by the return-light imaging unit, wherein in theimage-correction unit, a first exponent is obtained by a powerapproximation of a characteristic of luminance versus distance from theillumination portion to the subject, for the fluorescence image acquiredby the fluorescence-imaging unit when the excitation light of aprescribed luminance is radiated towards the subject; a second exponentis obtained by a power approximation of a characteristic of luminanceversus distance from the illumination portion to the subject, for areference image acquired by a return-light imaging unit when theillumination light of a prescribed intensity is radiated towards thesubject; a correction reference image is obtained by raising theluminance value of the reference image to the power of a third exponentthat is obtained by dividing the first exponent by the second exponent;a correction fluorescence image is obtained by dividing the fluorescenceimage by the correction reference image, or by raising the luminancevalue of the fluorescence image to the power of a fourth exponent thatis obtained by dividing the second exponent by the first exponent; and acorrected fluorescence image is obtained by dividing the correctionfluorescence image by the reference image.
 2. A fluoroscopy apparatusaccording to claim 1, further comprising an image-acquisition conditionadjusting portion that adjusts an image acquisition condition on thebasis of the luminance value of the fluorescence image acquired by thefluorescence-imaging unit, wherein the image-correction unit normalizesthe luminance of the fluorescence image by the image acquisitioncondition.
 3. A fluoroscopy apparatus according to claim 2, wherein theimage-acquisition condition adjusting portion adjusts an exposure timeof the fluorescence-imaging unit, and the image-correction unit dividesthe luminance value of the fluorescence image by the exposure time.
 4. Afluoroscopy apparatus according to claim 2, wherein theimage-acquisition condition adjusting portion adjusts a gain factor ofthe fluorescence-imaging unit, and the image-correction unit divides theluminance value of the fluorescence image by the gain factor.
 5. Afluoroscopy apparatus according to claim 2, wherein theimage-acquisition condition adjusting portion adjusts excitation-lightintensity from the illumination portion, and the image-correction unitdivides the luminance value of the fluorescence image by theexcitation-light intensity.
 6. A fluoroscopy apparatus according toclaim 1 further comprising an image-acquisition condition adjustingportion that adjusts the image acquisition condition on the basis of theluminance value of the reference image acquired by the return-lightimaging unit, wherein the image-correction unit normalizes the luminanceof the reference image by the image acquisition condition.
 7. Afluoroscopy apparatus according to claim 6, wherein theimage-acquisition condition adjusting portion adjusts an exposure timeof the return-light imaging unit, and the image-correction unit dividesthe luminance value of the reference image by the exposure time.
 8. Afluoroscopy apparatus according to claim 6, wherein theimage-acquisition condition adjusting portion adjusts a gain factor ofthe return-light imaging unit, and the image-correction unit divides theluminance value of the reference image by the gain factor.
 9. Afluoroscopy apparatus according to claim 6, wherein theimage-acquisition condition adjusting portion adjusts illumination lightintensity from the illumination portion, and the image-correction unitdivides the luminance value of the reference image by the illuminationlight intensity.
 10. A fluoroscopy system comprising a fluoroscopyapparatus according to claim 1 and a calibration device that calibratesthe fluoroscopy apparatus, wherein the calibration device is providedwith a standard specimen and an observation-state setting mechanism thatchangeably sets an observation distance of the fluoroscopy apparatusrelative to the standard specimen, and wherein the fluoroscopy apparatusor the calibration device is provided with an exponent calculating unitthat calculates the first exponent and the second exponent on the basisof the observation distance set by the observation-state settingmechanism and the fluorescence image and the reference image acquired byimaging the standard specimen with the fluoroscopy apparatus.